The present invention relates to a process for preparing adenine, and more particularly to a process for preparing adenine by thermally reacting an arylazomalononitrile of the general formula (I): ##STR1## wherein Ar is an aryl group, with formic acid or its derivatives in the presence of ammonia, and subjecting the resulting pyrimidine derivative to catalytic reduction substantially in the absence of ammonia.
Hitherto, there are known processes for the preparation of adenine using the arylazomalononitrile [I] as a starting material, e.g. in Examined Japanese Patent Publication (Tokkyo Kokoku) No. 23516/1976, Unexamined Japanese Patent Publication (Tokkyo Kokai) No. 81394/1974 and U.S. Pat. No. 4,092,314.
Japanese Patent Publication No. 23516/1976 discloses a process for preparing adenine in a single process step, in which adenine is prepared by reacting an arylazomalononitrile with a forming acid derivative in the presence of ammonia under a catalytic reduction condition. Japanese Patent Publication No. 81394/1974 and U.S. Pat. No. 4,092,314 disclose a process for preparing adenine in two process steps, in which an arylazomalononitrile is first thermally reacted with a forming acid derivative in the presence of ammonia to produce a pyrimidine derivative of the general formula (II): ##STR2## wherein Ar is an aryl group, and after isolating the pyrimidine derivative (II) or without conducting the isolation, the pyrimidine derivative (II) is subsequently reacted with a formic acid derivative under a catalytic reduction condition. In the reaction of the second step under catalytic reduction condition, hydrogenation of the pyrimidine derivative (II) and ring closure reaction of the resulting triaminopyrimidine take place.
These processes are superior to previously known processes for the preparation of adenine, but are now always satisfactory in the yield and purity of the obtained crude adenine. That is to say, the former process of one stage is simple in procedure, but the yield and purity are insufficient. In the latter process of two stages, adenine of a good purity is obtained in a good yield when the pyrimidine derivative (II) is once isolated and the reaction under catalytic reduction condition is then carried out, but the isolation procedure is very troublesome and is hard to apply to industrial preparation. When the reaction of the second step is successively carried out without taking out the pyrimidine derivative (II) from the reaction system, the yield and purity of the obtained adenine are not sufficient, and also it is hard to obtain adenine in a constant yield. In these known processes, amorphous greenish gray materials are by-produced as impurities, thus resulting in lowering of the yield and purity of the product.
The thus produced crude adenine has been generally purified in a manner in which a mixture of the crude adenine and water, e.g. water 40 and 50 times the amount of adenine, is refluxed to dissolve adenine and then decolored with an adsorbent such as active carbon. As special instances of purification, there are also known a process in which adenine is adsorbed by passing through a column of active carbon and is eluted with aqueous ammonia; a process using a cation-exchange resin (e.g. commercially available under the commercial name "Amberlite IR-120B" made by Rohm & Haas Co.); and a process in which impurities are oxidatively decomposed with potassium permanganate under an acidic condition to remove them and decoloration is then conducted with active carbon. Purification by sublimation is also proposed.
However, these purification processes are not satisfactory processes. In case of the above-mentioned general purification process by refluxing of a mixture of crude adenine and water followed by decoloration with active carbon, the purifity and whiteness are insufficient, and the other purification processes also have problems in purity, purification loss and cost.